Legal claims defining the scope of protection, as filed with the USPTO.
2. The assay of claim 1, wherein the functional metabolic change comprises a change from glucose and glycolysis dependent anabolism and energy metabolism to fatty acid uptake and fatty acid oxidation dependent anabolism and energy metabolism.
3. The assay of claim 1, wherein the metabolic index correlates to resistance to the therapy in the target cell or tissue when the functional metabolic change is a decrease in glucose and glycolysis dependent anabolism and an increase in fatty acid uptake and fatty acid oxidation dependent anabolism and energy metabolism.
4. The assay of claim 3, wherein the metabolic index further correlates to resistance to the therapy in the target cell or tissue when the metabolic change is a decrease in de novo lipogenesis in the target cell or tissue.
5. The assay of claim 1, wherein the metabolic index is a ratio of an increase in fatty acid uptake and oxidation to a decrease in glucose-dependent anabolism.
6. The assay of claim 1, wherein measuring with chemical microscopy functional metabolic change comprises measuring glucose and glycolysis derived anabolism in the target cell or tissue, measuring fatty acid uptake and oxidation in the target cell or tissue, and determining a change from glucose anabolism in the target cell or tissue to fatty acid uptake and oxidation energy metabolism.
7. The assay of claim 6, further comprising measuring de novo lipogenesis in the target cell or tissue, and determining a change from glucose and glycolysis dependent anabolism and de novo lipogenesis in the target cell or tissue to fatty acid uptake and oxidation energy metabolism.
8. The assay of claim 1, wherein the chemical microscopy comprises Raman microscopy or infrared microscopy.
9. The assay of claim 1, wherein the target cell induces cellular stress in the target cell or tissue.
10. The assay of claim 1, wherein the cellular stress in the target cell or tissue is oxidative stress, metabolic stress, hypoxic stress, nutrient stress, thermal stress, genotoxic stress, or combinations thereof.
11. The assay of claim 1, wherein the target cell or tissue is a cancer cell, and the therapy is a cancer therapy.
12. The assay of claim 11, wherein the cancer therapy is selected from chemotherapy, radiotherapy, immunotherapy, targeted therapy, hormone therapy, light or laser therapy, photodynamic therapy, and combinations thereof.
13. The assay of claim 12, wherein the chemotherapy is a platinum-based therapeutic selected from cisplatin, carboplatin, oxaliplatin, nedaplatin, and combinations thereof.
15. The method of claim 14, wherein measuring with chemical microscopy functional metabolic change comprises measuring glucose and glycolysis derived anabolism in the cancer cell, measuring fatty acid uptake and oxidation in the target cell or tissue, and the metabolic index is the ratio of an increase in fatty acid uptake and oxidation energy metabolism to a decrease in glucose and glycolysis derived anabolism in the target cell or tissue.
16. The method of claim 14, wherein performing the assay of claim 1 further comprises obtaining a target cell or tissue from the subject.
17. The method of claim 14, wherein the target cell is a cancer cell, and the therapy is a cancer therapy.
18. The method of claim 14, wherein determining the metabolic index of resistance in the target cell or tissue to the therapy further includes a decrease in de novo lipogenesis.
19. The method of claim 14, wherein fatty acid oxidation is inhibited in the target cell or tissue and the therapy induces cellular stress in the target cell or tissue, thereby inhibiting resistance to the therapy.
20. The method of claim 14, wherein the at least one inhibitor of fatty acid oxidation is selected from etomoxir, oxfenicine, perhexiline, mildronate, trimetazidine, and combinations thereof.
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July 4, 2023
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